rs4389093

Variant names:

• chr15-49450872-A-G
• rs4389093
• NM_152647.3:c.1012+57339T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152647.3(FAM227B):​c.1012+57339T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,050 control chromosomes in the GnomAD database, including 6,915 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (6915 hom., cov: 32)
• Consequence: FAM227B NM_152647.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.727
• Publications: 3 publications found

Genes affected

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

FGF7 (HGNC:3685): (fibroblast growth factor 7) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein is a potent epithelial cell-specific growth factor, whose mitogenic activity is predominantly exhibited in keratinocytes but not in fibroblasts and endothelial cells. Studies of mouse and rat homologs of this gene implicated roles in morphogenesis of epithelium, reepithelialization of wounds, hair development and early lung organogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM227B	NM_152647.3	c.1012+57339T>C		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2
FGF7	NM_002009.4	c.286+26289A>G		intron_variant	Intron 2 of 3	ENST00000267843.9	NP_002000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM227B	ENST00000299338.11	c.1012+57339T>C		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6
FGF7	ENST00000267843.9	c.286+26289A>G		intron_variant	Intron 2 of 3	1	NM_002009.4	ENSP00000267843.4

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41511 AN: 151932 Hom.: 6914 Cov.: 32

Gnomad AFR AF: 0.0889

Gnomad AMI AF: 0.517

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.289

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.273 AC: 41494 AN: 152050 Hom.: 6915 Cov.: 32 AF XY: 0.271 AC XY: 20165 AN XY: 74304

African (AFR) AF: 0.0888 AC: 3686 AN: 41530

American (AMR) AF: 0.266 AC: 4050 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1500 AN: 3468

East Asian (EAS) AF: 0.186 AC: 963 AN: 5176

South Asian (SAS) AF: 0.210 AC: 1011 AN: 4812

European-Finnish (FIN) AF: 0.338 AC: 3579 AN: 10580

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25557 AN: 67920

Other (OTH) AF: 0.285 AC: 602 AN: 2114

Alfa AF: 0.318 Hom.: 1076

Bravo AF: 0.260

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.0
DANN	Benign	0.78
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4389093; hg19: chr15-49743069;